Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST).
OBJECTIVE
The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in randomized, controlled trials (RCTs) when used in routine clinical practice within 3 hours of ischemic stroke onset. We aimed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs.


METHODS
The study population was SITS-MOST (n=6483) and pooled RCTs (n=464) patients treated with intravenous alteplase within 3 hours of stroke onset. Multivariable, backward stepwise regression analyses (until P<or=0.10) were performed to identify the outcome predictors for SITS-MOST. Variables appearing either in the final multivariable model or differing (P<0.10) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes. Main outcome measures were symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale deterioration >or=1 within 7 days with any hemorrhage (RCT definition), mortality, and independency as defined by modified Rankin Score of 0 to 2 at 3 months.


RESULTS
The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5% (95% CI, 7.9 to 9.0) versus 8.6% (6.3 to 11.6) for pooled RCTs; mortality was 15.5% (14.7 to 16.2) versus 17.3% (14.1 to 21.1); and independency was 50.4% (49.6 to 51.2) versus 50.1% (44.5 to 54.7), respectively. In the multivariable analysis, older age, high blood glucose, high National Institutes of Health Stroke Scale score, and current infarction on imaging scans were related to poor outcome in all parameters. Systolic blood pressure, atrial fibrillation, and weight were additional predictors of symptomatic intracerebral hemorrhage. Current smokers had a lower rate of symptomatic intracerebral hemorrhage. Disability before current stroke (modified Rankin Score 2 to 5), diastolic blood pressure, antiplatelet other than aspirin, congestive heart failure, patients treated in new centers, and male sex were related to high mortality at 3 months.


CONCLUSIONS
The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis. We identified several important outcome predictors to better identify patients suitable for thrombolysis.
Wahlgren
Nils
N
Department of Neurology, Karolinska University Hospital-Solna, Karolinska Institutet, Stockholm, Sweden. nils.wahlgren@karolinska.se
Ahmed
Niaz
N
Eriksson
Niclas
N
Aichner
Franz
F
Bluhmki
Erich
E
Dávalos
Antoni
A
Erilä
Terttu
T
Ford
Gary A
GA
Grond
Martin
M
Hacke
Werner
W
Hennerici
Michael G
MG
Kaste
Markku
M
Köhrmann
Martin
M
Larrue
Vincent
V
Lees
Kennedy R
KR
Machnig
Thomas
T
Roine
Risto O
RO
Toni
Danilo
D
Vanhooren
Geert
G
D000203:Activities of Daily Living; D000368:Aged; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D015897:Comorbidity; D003953:Diagnosis-Related Groups; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018579:Patient Selection; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012042:Registries; D012307:Risk Factors; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000706:statistics & numerical data*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator